Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS One. 2013;8(2):e55828. doi: 10.1371/journal.pone.0055828. Epub 2013 Feb 14.
Neogenin has been implicated in a variety of developmental processes such as neurogenesis, neuronal differentiation, apoptosis, migration and axon guidance. Binding of repulsive guidance molecules (RGMs) to Neogenin inhibits axon outgrowth of different neuronal populations. This effect requires Neogenin to interact with co-receptors of the uncoordinated locomotion-5 (Unc5) family to activate downstream Rho signaling. Although previous studies have reported RGM, Neogenin, and/or Unc5 expression, a systematic comparison of RGM and Neogenin expression in the developing nervous system is lacking, especially at later developmental stages. Furthermore, information on RGM and Neogenin expression at the protein level is limited. To fill this void and to gain further insight into the role of RGM-Neogenin signaling during mouse neural development, we studied the expression of RGMa, RGMb, Neogenin and Unc5A-D using in situ hybridization, immunohistochemistry and RGMa section binding. Expression patterns in the primary olfactory system, cortex, hippocampus, habenula, and cerebellum were studied in more detail. Characteristic cell layer-specific expression patterns were detected for RGMa, RGMb, Neogenin and Unc5A-D. Furthermore, strong expression of RGMa, RGMb and Neogenin protein was found on several major axon tracts such as the primary olfactory projections, anterior commissure and fasciculus retroflexus. These data not only hint at a role for RGM-Neogenin signaling during the development of different neuronal systems, but also suggest that Neogenin partners with different Unc5 family members in different systems. Overall, the results presented here will serve as a framework for further dissection of the role of RGM-Neogenin signaling during neural development.
Neogenin 参与了多种发育过程，如神经发生、神经元分化、细胞凋亡、迁移和轴突导向。排斥性导向分子（RGMs）与 Neogenin 的结合抑制了不同神经元群体的轴突生长。这种效应需要 Neogenin 与未协调运动-5（Unc5）家族的共受体相互作用，以激活下游 Rho 信号转导。尽管先前的研究已经报道了 RGM、Neogenin 和/或 Unc5 的表达，但缺乏对发育中神经系统中 RGM 和 Neogenin 表达的系统比较，特别是在后期发育阶段。此外，关于 RGM 和 Neogenin 在蛋白质水平表达的信息也很有限。为了填补这一空白，并进一步深入了解 RGM-Neogenin 信号在小鼠神经发育中的作用，我们使用原位杂交、免疫组织化学和 RGMa 切片结合法研究了 RGMa、RGMb、Neogenin 和 Unc5A-D 的表达。更详细地研究了初级嗅觉系统、皮质、海马、缰核和小脑的表达模式。检测到 RGMa、RGMb、Neogenin 和 Unc5A-D 的特征细胞层特异性表达模式。此外，在主要的轴突束如初级嗅觉投射、前连合和折返束上发现了 RGMa、RGMb 和 Neogenin 蛋白的强烈表达。这些数据不仅暗示了 RGM-Neogenin 信号在不同神经元系统发育中的作用，还表明 Neogenin 在不同系统中与不同的 Unc5 家族成员结合。总的来说，这里呈现的结果将为进一步解析 RGM-Neogenin 信号在神经发育中的作用提供框架。
